BIOTECH: Embryonic stem cell breakthrough gains support

No embryos needed with new technology

Human embryonic stem cells, now obtained from embryos, soon may
be routinely produced from a much less controversial source: Skin
cells. Certain chemicals and genes added to the adult human cells
reprogram them to an embryonic-like state.

The reprogramming breakthrough, announced last November, has
since been confirmed by scientists around the world. Top
researchers, including those in San Diego County's large community
of stem cell scientists, say they're increasingly confident that
use of these reprogrammed, or "induced pluripotent cells", will
replace stem cells derived from embryos.

And perhaps most significantly, this advance removes the biggest
ethical objections to stem cell technology: the use of embryos,
which many consider to be human life. The new technology doesn't
use embryos.

"My personal feeling, and the scientific evidence so far, is
that making human stem cells will in fact take over the embryonic
stem cells space," said Jeanne Loring, a noted stem cell researcher
at The Scripps Research Institute in La Jolla. The cells are of
interest for their potential in treating now incurable diseases and
injuries.

Use of reprogrammed cells has already been accepted by the Roman
Catholic Church, a leading opponent of using human embryos for
research. And because skin cells are far easier to get than
embryos, scientists say a major research bottleneck will be
removed.

Stem cell scientists will be busier than ever exploring the new
possibilities, said Evan Snyder, a prominent stem cell researcher
at the Burnham Institute, also in La Jolla.

"Right now, I would say nothing is off the table," said
Snyder.

Snyder said he was skeptical of the technology, and still has
residual doubts. He urged researchers to go back and re-examine
earlier studies that ruled out adult cell reprogramming.

"These guys were not stupid and they're not lying," Snyder said
of those performing the earlier studies. However, perhaps some
errors or faulty assumptions crept in.

That expanded research agenda implies a lot of money will be
needed, and California's $3 billion stem cell program is preparing
for the challenge. It has already asked for researchers to submit
funding proposals to explore the new technology.

Many scientists think embryonic stem cells, the "ancestral"
cells that turn into the specialized cells of the body, could be
used to make replacement tissue, such as insulin-producing cells in
the pancreas, or nerve cells to heal a damaged spinal cord. They
could also be used as "screens" to test the effect of experimental
drugs on human cells before they are tested in human patients.

Until the skin-cell breakthrough, these cells only were
obtainable from embryos.

Removing a bottleneck

But limited availability of embryonic stem cells and funding
restrictions have hobbled research. Available embryos are hard to
come by, for one thing, and the consent of the parents generally
must be obtained. Most embryos used are leftovers from in vitro
fertilization.

Citing ethical concerns because human embryos are killed to get
the cells, President Bush has allowed only very limited federal
funding of this research. That prompted voters to approve
California's $3 billion stem cell research program, which until
last year was itself hobbled by court battles over its
legality.

With the program's legality established, and an infinite new
source of embryonic stem cells likely, those concerns are fast
being resolved. It is morally permissible to use the reprogrammed
cells, said Stephen Napier, a staff ethicist at the National
Catholic Bioethics Center, which reflects official Catholic
teaching.

"In the case of embryonic stem cells, a human embryo is
destroyed to derive the stem cell lines, whereas in induced
pluripotent stem cells, never at any point do you have a human
being," Napier said.

However, researchers Snyder and Loring said that while the
artificial embryonic stem cells appear to act like the natural
kind, this has to be further confirmed before they can be ethically
used in people. That means natural embryonic stem cells must be
tested against the artificial kind until all doubts have been
resolved.

Moreover, other ethical questions about embryonic stem cell
therapy will arise as research gets closer to human treatments,
said Arthur Caplan and Michael Kalichman, two experts on
bioethics.

One is ensuring that the poor have access to the treatments,
especially in California, which is spending public funds on the
research, said Caplan, director of the Center for Bioethics at the
University of Pennsylvania in Philadelphia.

A second concern is balancing the concerns of medical science
with the desire of desperately ill patients to get these treatments
as soon as possible.

"People are going to say, 'I don't need to go through all those
animal studies. I'm dying. Let's go,' " Caplan said. It's important
to continue studying these treatments in a "controlled" fashion so
doctors learn about any potential negative effects, he said.

"Even if you're dying, you can die faster," Caplan said. "Even
if you're dying, you can die more miserably. We need to know
that."

Like Snyder and Loring, Kalichman said research with natural
human embryonic stem cells will be needed for some time to validate
the artificial stem cells, and that means the ethical concerns over
using human embryos will be around for that duration.

"Scientifically, we don't yet have an end run," Kalichman said.
"The only way you can develop any reasonable confidence about what
you have will be to compare … We're not done yet."

Other ethical questions arise when human stem cells are
implanted in animals, a necessary part of research to determine how
these cells work in a living creature, Kalichman said.

"If I really want to know if my pluripotent stem cell really can
become a liver cell, or a kidney cell or a brain cell; it's going
to be very hard to put that into a human as your first experiment,"
Kalichman said.

However, creating such a mixed-cell animal, or "chimera," has
caused ethical objections in some quarters. In his 2006 State of
the Union address, President Bush asked Congress to ban
human-animal hybrids.

Business competition

Despite the numerous ethical issues, a growing number of
biotechnology companies have formed around stem cell therapy.

Many are developing alternatives to using natural embryonic stem
cells. These include Oceanside's International Stem Cell Corp.,
which has produced act-alike embryonic stem cells from
parthenogenetic, or unfertilized, human egg cells.

Other companies are avoiding embryonic stem cells entirely, by
working with stem cells found in adults. These include Cytori, a
San Diego-based company that harvests stem cell from fat cells.

A new company working on induced pluripotent stem cells, iZumi
Bio Inc., announced a research agreement with the San
Francisco-based J. David Gladstone Institutes last month. The
company is funded by the renowned venture capital firm Kleiner
Perkins Caufield & Byers.

Kleiner Perkins has been involved in biotechnology for decades.
Three decades ago, it funded a biotech startup called Hybritech,
San Diego's first biotech company.